Schwartz-Jampel syndrome, Type 1

What is Schwartz-Jampel syndrome, Type 1?

It is a rare genetic syndrome that affects mainly the skeletal muscles.
There are two types of the syndrome, with Type 1 being the most common form of the syndrome, with symptoms that are usually first identified in late infancy or early childhood.

There are 85 cases reported of the syndrome so far.

This syndrome is also known as:
Chondrodystrophic Myotonia Myotonic Myopathy, Dwarfism, Chondrodystrophy, And Ocular And Facial Abnormalities Schwartz-jampel Syndrome; Sjs Schwartz-jampel-aberfeld Syndrome Sja Syndrome

What gene changes cause Schwartz-Jampel syndrome, Type 1?

It is believed that the syndrome is caused by changes of a gene that encodes perlecan on the short arm of chromosome 1, this is the HSPG2 gene.

The syndrome is inherited in an autosomal recessive pattern.

What are the main symptoms of Schwartz-Jampel syndrome, Type 1?

Symptoms may vary in affected individuals but the main symptoms of the syndrome mainly affect the skeletal muscle, bone and cartilage. These include muscle weakness, stiffness and joint contractures (where the joins are permanently bent or straightened). Very small skeletal muscles are also common with the syndrome.
Eye anomalies and abnormalities are also common with the condition.
Growth delay is also associated with the syndrome.
Developmental delays are common, especially in the toddler years. These delays mainly affect the development of gross motor skills- crawling, walking, running.
Unique facial features of the syndrome include a very small mouth and chin, low set ears, a flat face, mask-like facial expressions that seem fixed.

Possible clinical traits/features:
Cognitive impairment, Hip contracture, High pitched voice, Prominent nasal bridge, Hyporeflexia, Visual impairment, Kyphosis, Hypertrichosis, Hypertonia, Hypertelorism, Hyperlordosis, Short stature, Genu valgum, Flexion contracture of toe, Gait disturbance, Generalized hirsutism, Full cheeks, Arthrogryposis multiplex congenita, Decreased body weight, Microcornea, Coxa vara, Coxa valga, Coronal cleft vertebrae, EMG abnormality, Ectopia lentis, Congenital hip dislocation, Sprengel anomaly, Distichiasis, Delayed skeletal maturation, Myotonia, Malar flattening, Limitation of joint mobility, Decreased testicular size, Wrist flexion contracture, Feeding difficulties in infancy, Everted lower lip vermilion, Elbow dislocation, Anterior bowing of long bones, Skeletal muscle atrophy, Polyhydramnios, Cleft palate, Cataract, Attention deficit hyperactivity disorder, Blepharophimosis, Aplasia/Hypoplasia affecting the eye, Apnea, Abnormality of the ribs, Abnormality of the pharynx, Abnormality of the metaphysis, Abnormally

How does someone get tested for Schwartz-Jampel syndrome, Type 1?

The initial testing for Schwartz-Jampel syndrome, Type 1 can begin with facial analysis screening, through the FDNA Telehealth telegenetics platform, which can identify the key markers of the syndrome and outline the need for further testing. A consultation with a genetic counselor and then a geneticist will follow.

Medical information on Schwartz-Jampel syndrome, Type 1

Syndrome Overview:
Schwartz-Jampel syndrome, Type 1 is an autosomal recessive disorder that features myotonic myopathy, osteochondrodysplasia, and a “fixed” or ""mask-like"" facial expression (narrow palpebral fissures, blepharospasm, pursed lips). Schwartz-Jampel syndrome, Type 1 is caused by mutations in the HSPG2 gene.

This condition appears primarily to be a form of myotonic myopathy with an associated chondrodysplasia. Blepharophimosis, difficulty in opening the mouth, an expressionless face, ptosis, muscle wasting with myotonia, multiple joint contractures and joint limitation all suggest an underlying abnormality of muscle.

The differential diagnosis includes Marden-Walker and Freeman-Sheldon syndromes.

Schwartz-Jampel syndrome, Type 1 is subcategorized into two types. Type 1a has a milder phenotype, with relatively reduced chondrodysplasia and an onset ranging from infancy to early childhood. Type 1b has a more severe phenotype including neonatal onset and significant chondrodysplasia, reminiscent of Kniest dysplasia (Giedion et al., 1997).
Skeletal abnormalities include short stature, kyphoscoliosis, lumbar lordosis, pectus carinatum, bowing of the long bones, pes planus, a valgus deformity of the ankles and wide metaphyses. Radiographs show platyspondyly, coronal clefts of the vertebral bodies and an epiphyseal dysplasia, especially around the hips. Repetitive discharges on electromyography (EMG) are characteristic. Persistent spontaneous activity, particularly in the face and thigh muscles, is often reduced at rest. Ocular abnormalities such as microphthalmia or cataracts have been reported.

Seay et al., (1978) reported a patient who suffered malignant hyperpyrexia after ketamine, nitrous oxide and curare anesthesia.

Some cases present during the neonatal period with feeding and respiratory difficulties. Al-Gazali et al., (1996) review 11 cases with this presentation. Nine died from respiratory complications before 2 years of age. Topaloglu et al., (1993) reported improvement of myotonia in three cases treated with carbamazepine. Squires and Prangley (1996) also reported a neonatal case that responded favorably to carbamazepine. Spaans et al., (1991) reported improvement in muscle symptoms after treatment with procainamide.

Figuera et al., (1993) reported a case without skeletal anomalies and postulated a milder form of the disorder. In addition, Moodley and Moosa (1990) reported a case with skeletal and clinical features of the condition but without clinical or electrophysiological evidence of myotonia.

Nicole et al., (1995) localized the gene to 1p34-p36 in recessive Type 1a families. Refined localization was reported by Fontaine et al., (1996). Nicole et al., (2000) then demonstrated missense and splicing mutations in the HSPG2 gene encoding the perlecan protein in Type 1a.

Arikawa-Hirasawa et al., (2002) studied three unrelated patients with Schwartz-Jampel syndrome. Heterozygous mutations were found in two patients producing a truncated perlecan that lacked domain V or significantly reduced levels of wild-type perlecan. The other patient had a homozygous 7-kb deletion that resulted in reduced amounts of nearly full-length perlecan.

Stum et al., (2006) reviewed HSPG2 mutations in 23 affected families, finding wide variability in mutation type. There were nine deletion or insertion (41%), six splice site (27%), five missense (23%) and two nonsense mutations (9%).

A series of six Type 1a cases described by Arya, et al. (2013) demonstrates the wide variability in clinical presentation in Schwartz-Jampel syndrome, Type 1. No clear genotype-phenotype correlation has been observed.

Iwata et al., (2015) described a male patient with rigid walking and dysmorphic features with biallelic mutations in the HSPG2 gene. Clinical characteristics included whistling-like face, blepharophimosis, flexion posture, hypertonia, myotonia and mild chondrodysplasia. EMG showed bursts of recurrently firing complex muscle action potentials with fixed frequency, and muscle biopsy showed fiber size variation, pyknotic nuclear clumps, necrotic fibers and phagocytosis.

Dai et al., (2015) reported two novel HSPG2 variants in a Chinese girl with Schwartz-Jampel syndrome, Type 1.

A novel homozygous intronic splice site mutation was reported by Das Bhowmik et al., (2016) in a patient with clinical features of Schwartz-Jampel syndrome, Type 1.

Mathur and Ghosh (2017) focused on evolution of dysmorphic features (blepharophimosis, low-set ears, pursed lips and apparent tearful face when asked to smile) in a girl with homozygous mutations in the HSPG2 gene.

Bandeira et al., (2017) described the positive response of facial myotonia to botulinum toxin type A injections in two female patients with Schwartz-Jampel syndrome, Type 1.

* This information is courtesy of the L M D.
If you find a mistake or would like to contribute additional information, please email us at: [email protected]

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